Varma Ankur, Biritxinaga Laura, Saliba Rima M, Stich Maximilian, Jauch Sarah Francesca, Afrough Aimaz, Honhar Medhavi, Popat Uday R, Shafi Mehnaz A, Shah Nina, Bashir Qaiser, Dinh Yvonne, Hosing Chitra, Champlin Richard E, Qazilbash Muzaffar H
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas; Department of Medicine, Section of Hematology and Oncology, Baylor College of Medicine, Houston, Texas.
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Biol Blood Marrow Transplant. 2017 Apr;23(4):581-587. doi: 10.1016/j.bbmt.2017.01.005. Epub 2017 Jan 4.
Hepatitis B core antibody (HBcAb) seropositivity has been associated with a higher rate of hepatitis B virus (HBV) reactivation after chemotherapy, even in patients who are hepatitis B surface antigen (HBsAg) negative. However, little is known about the risk of HBV reactivation after autologous hematopoietic stem cell transplantation (auto-HCT). We evaluated the incidence of HBV reactivation, liver toxicity, and survival in patients with multiple myeloma (MM) who received auto-HCT at our institution. We retrospectively identified 107 MM patients with resolved HBV infection (HBcAb positive, HBsAg negative) and 125 patients with negative HBV serology (control subjects) who were matched for age, timing of auto-HCT from diagnosis, cytogenetics, disease status at transplant, induction therapy, and preparative regimen. All patients underwent auto-HCT between 1991 and 2013. Primary endpoints were HBV reactivation, defined as HBsAg positivity or ≥10-fold increase in HBV DNA, and hepatotoxicity, as defined in the U.S. National Cancer Institute Common Terminology Criteria for Adverse Events v3.0. In the resolved HBV infection group, 52 patients (49%) were HBsAb positive and 24 (22%) had detectable HBV DNA before auto-HCT. Only 1 patient with resolved HBV infection received pre-emptive antiviral therapy with lamivudine, whereas 4 patients received lamivudine (n = 3) or tenofovir (n = 1) at reactivation after auto-HCT for a median duration of 12 months. HBV reactivation occurred in 7 of 107 patients (6.5%) in the resolved HBV group. Median time to HBV reactivation from auto-HCT was 16 months. The cumulative incidence of grade 2 or greater hepatotoxicity was 30% in the resolved HBV infection group and 22% in the control group (hazard ratio, 1.3; 95% confidence interval, .7 to 2.3; P = .4). Nonrelapse mortality for the 2 groups was not statistically different at 2 years (P = .06), although it trended higher in the control group than in the resolved HBV infection group (8% versus 1%). The median progression-free survival (PFS) and overall survival (OS) durations in the resolved HBV infection and control groups were 21 versus 18 months (P = .5) and 53 versus 67 months (P = .2), respectively. Our data suggest that resolved HBV infection in patients undergoing auto-HCT for MM is associated with a low risk of HBV reactivation and hepatotoxicity; these complications were reversible and did not adversely affect the PFS or OS.
乙肝核心抗体(HBcAb)血清学阳性与化疗后较高的乙肝病毒(HBV)再激活率相关,即使是乙肝表面抗原(HBsAg)阴性的患者。然而,对于自体造血干细胞移植(auto-HCT)后HBV再激活的风险知之甚少。我们评估了在本机构接受auto-HCT的多发性骨髓瘤(MM)患者中HBV再激活、肝毒性和生存率。我们回顾性地确定了107例已解决HBV感染(HBcAb阳性,HBsAg阴性)的MM患者和125例HBV血清学阴性的患者(对照受试者),这些患者在年龄、自诊断起的auto-HCT时间、细胞遗传学、移植时的疾病状态、诱导治疗和预处理方案方面相匹配。所有患者在1991年至2013年期间接受了auto-HCT。主要终点是HBV再激活,定义为HBsAg阳性或HBV DNA增加≥10倍,以及肝毒性,按照美国国立癌症研究所不良事件通用术语标准v3.0进行定义。在已解决HBV感染组中,52例患者(49%)HBsAb阳性,24例(22%)在auto-HCT前可检测到HBV DNA。只有1例已解决HBV感染的患者接受了拉米夫定的抢先抗病毒治疗,而4例患者在auto-HCT后再激活时接受了拉米夫定(n = 3)或替诺福韦(n = 1),中位持续时间为12个月。在已解决HBV感染的107例患者中,有7例(6.5%)发生了HBV再激活。从auto-HCT到HBV再激活的中位时间为16个月。在已解决HBV感染组中,2级或更高级别肝毒性的累积发生率为30%,对照组为22%(风险比,1.3;95%置信区间,0.7至2.3;P = 0.4)。两组的非复发死亡率在2年时无统计学差异(P = 0.06),尽管对照组的趋势高于已解决HBV感染组(8%对1%)。已解决HBV感染组和对照组的中位无进展生存期(PFS)和总生存期(OS)分别为21个月对18个月(P = 0.5)和53个月对67个月(P = 0.2)。我们的数据表明,接受MM auto-HCT的患者中已解决的HBV感染与HBV再激活和肝毒性的低风险相关;这些并发症是可逆的,且对PFS或OS没有不利影响。